A combination of a common diabetes medication and a drug for treating hypertension may effectively combat a wide range of cancer cells by driving them to commit ‘suicide’, a new study has claimed.
Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. Besides its blood sugar lowering effect, it also displays anti-cancer properties. The usual therapeutic dose is too low to effectively fight cancer. Researchers, led by Michael Hall from the University of Basel in Switzerland, found that antihypertensive drug syrosingopine potentiates the anti-cancer efficacy of metformin.
The drug combination drives cancer cells to programmed “suicide.” At higher doses, the antidiabetic drug inhibits the growth of cancer cells but could also induce unwanted side effects. Researchers screened over a thousand drugs for whether they can enhance the anticancer action of metformin.
The cocktail with syrosingopine effective in a wide range of cancers, researchers said. “For example, in samples from leukaemia patients, we demonstrated that almost all tumour cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” said Don Benjamin, from the University of Basel.
“And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment,” Benjamin said. In mice with malignant liver cancer, enlargement of the liver was reduced after the therapy. Also the number of tumour nodules was less – in some animals the tumours disappeared completely.
A glance at the molecular processes in the tumour cells explains the drug combination’s efficacy: Metformin lowers not only the blood glucose level, but also blocks the respiratory chain in the energy factories of the cell, the mitochondria.
The antihypertensive drug syrosingopine inhibits, among other things, the degradation of sugars. Thus, the drugs interrupt the vital processes which provide energy for the cell. Due to their increased metabolic activity and rapid growth, cancer cells have a particularly high energy consumption, which makes them extremely vulnerable when the energy supply is reduced.
By testing a range of other compounds with the same mode of action, the scientists could demonstrate that the inhibition of the respiratory chain in the mitochondria is a key mechanism. These also reduced cancer cell growth in combination with the antihypertensive drug.
“We have been able to show that the two known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” said Benjamin. “The data from this study support the development of combination approaches for the treatment of cancer patients,” he said.
The study was published in the journal Science Advances.